Impact of Obesity on the Pharmacokinetics of Imipenem-Relebactam in ICU Patients

This study is an open-label, multiple-dose pharmacokinetic study of imipenem-relebactam conducted in 12 non-infected, obese ICU patients.

Study Overview

• Status: Withdrawn
• Conditions: Obesity; Critical Illness
• Intervention / Treatment: Drug: Imipenem/Cilastatin/Relebactam 1.25g

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years of age
2. Admitted to the ICU
3. BMI ≥40 kg/m2 and/or total body weight ≥120 kg
4. Provide a signed and dated written informed consent prior to study participation

Exclusion Criteria:

1. History of significant hypersensitivity reaction or intolerance to imipenem/cilastatin or carbapenem-based agents (doripenem, ertapenem, or meropenem +/- vaborbactam)
2. History of seizures and/or receiving 1 or more anti-epileptic agent
3. Serum creatinine ≥1.5 mg/dL
4. Estimated creatinine clearance (CLCR) <60 mL/minute as determined by Cockcroft-Gault equation:
5. Actively receiving antimicrobial therapy for treatment of a confirmed or suspected infection
6. The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days prior to the first dose of study medication
7. Positive serum pregnancy test (for women of childbearing potential)
8. Currently breast feeding
9. Has previously participated in this study
10. Concomitant use of valproic acid or divalproex sodium
11. Any other condition that may make the patient unsuitable for the study in the judgement of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pharmacokinetic cohort; After at least 2 doses of study drug, serial blood samples will be collected from 12 non-infected, obese ICU patients to evaluate the pharmacokinetics of imipenem and relebactam in this population.	Drug: Imipenem/Cilastatin/Relebactam 1.25g; Imipenem/cilastatin/relebactam is a combination beta-lactam/beta-lactamase inhibitor antimicrobial marketed under the brand name Recarbrio and the approved dose is 1.25g Q6h in patients with normal renal function. The individual components of this agent must be administered together and cannot be separated. Therefore, this constitutes only one intervention. Each subject will receive at least 2 doses of study drug.; Other Names: Recarbrio
Experimental: Safety cohort; After at least 2 doses of study drug, safety will be monitored closely during study drug dosing and through 72 hours after the last dose is administered in the same 12 non-infected, obese ICU patients from the PK arm	Drug: Imipenem/Cilastatin/Relebactam 1.25g; Imipenem/cilastatin/relebactam is a combination beta-lactam/beta-lactamase inhibitor antimicrobial marketed under the brand name Recarbrio and the approved dose is 1.25g Q6h in patients with normal renal function. The individual components of this agent must be administered together and cannot be separated. Therefore, this constitutes only one intervention. Each subject will receive at least 2 doses of study drug.; Other Names: Recarbrio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters of imipenem and relebactam	Peak Plasma Concentration (Cmax)	6 months
Pharmacokinetic parameters of imipenem and relebactam	Area under the plasma concentration versus time curve (AUC)	6 months
Pharmacokinetic parameters of imipenem and relebactam	Total body clearance (CLt)	6 months
Pharmacokinetic parameters of imipenem and relebactam	Apparent volume of distribution (Vd)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of imipenem and relebactam	Monitoring for adverse drug events	6 months

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2023
• Primary Completion (Estimated): June 1, 2023
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: November 13, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Disease Attributes; Overnutrition; Body Weight; Overweight; Obesity; Critical Illness; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; beta-Lactamase Inhibitors; Imipenem; Relebactam; Cilastatin
• Other Study ID Numbers: 2021-1145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No